Oxytocin (OT) is well known for its role in reproduction. However, evidence has emerged suggesting a role in cardiovascular system. The aim of this study was to investigate the cardioprotective effect of oxytocin on ischemia/reperfusion (I/R) injury in an in vivo rat. Myocardial ischemia, was surgically induced by means of left anterior descending coronary artery occlusion for 25 min followed by reperfusion for 120 min. Infarct size was evaluated using the staining agent 2,3,5-triphenyltetrazolium chloride. Creatine kinase-MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH) levels in plasma were analyzed to assess the degree of cardiac injury. Intraperitoneal administration of OT 0.001, 0.01 and 0.1 microg significantly reduced infarct size, LDH and CK-MB levels as compared to control (I/R) group and it had a biphasic effect on the reduction of ischemia/reperfusion injury. This biphasic effect was revealed as a U-shaped curve in which efficacy was optimal between very low and very high doses. Furthermore there were no significant differences in mean arterial pressure or heart rate between the OT treatment groups and control group during I/R. Blockade of specific OT receptors by atosiban (10(-6)M) abolished or attenuated the effect of OT preconditioning. The result of this study shows that OT possess a dose-dependent cardioprotective effect against ischemia/reperfusion injury and so study of OT preconditioning may provide a new target site for therapeutic exploitation.